• Title/Summary/Keyword: Clinical pharmacogenomics

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Current Status of Herb-Drug Interaction Information and Information Database in Korea (국내 한약-양약 상호작용 연구논문 분석을 통한 상호작용 정보 현황파악 및 제공방안에 대한 연구)

  • Park, Soo-Jin;Kwon, Young-Kyu;Shin, Jae-Gook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.4
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    • pp.543-552
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    • 2010
  • The objectives of this study are to examine the current status and problems of herb-drug interaction (HDI) information and information database in Korea and suggest the better way to establish useful HDI database. We collected HDI studies that published in Korea and analyzed according to objective, methods, selection criteria of herbs, number of study, correlation between study subject and frequently used herbal medicine (HM). Then we selected representative HM database on the internet made by Korea Food and Drug Administration (KFDA) among the several databases and analyzed its contents related to HDI. Several HDI studies were carried out from laboratory based research to clinical trials and HM databases have been developed for providing information about different aspects of traditional Korean medicine. But the information of HDI and information database are still far from practical applications because there are no coherence to select study subjects and methods among researchers. So, it is necessary to build up HDI database led by the government for providing systematic HDI information. HDI information database is expected to be able to provide useful evidence for health professionals in prescription and consultation to reduce the chance of adverse effects and improve the quality of medical care.

Genetic Polymorphisms in Drug Transporters and Regulatory Xenobiotic Receptors in Korean Population

  • Lee, Sang-Seop;Shin, Jae-Gook
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2004.05a
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    • pp.27-29
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    • 2004
  • Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDR1 gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorphisms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.

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Genetic Polymorphisms in Drug Transporters and Regulatory Xenobiotic Receptors in Korean Population

  • Lee, Sang-Seop;Shin, Jae-Gook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2004.05a
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    • pp.27-29
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    • 2004
  • Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDRl gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorph isms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.

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Differential Behaviour of Selenium Analogs against Anticancer Drug Induced Apoptosis of Lymphocytes in Human Peripheral Blood

  • Elango, Sonaa;Subbiah, Usha;Jain, Jeong
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.5
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    • pp.2527-2533
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    • 2016
  • Sensitising cancer cells and at the same time desensitizing normal cells is a double task in cancer management. Agents which can combat the debilitating side effects of cancer therapeutics and simultaneously synergize with anticancer agents in specifically targeting cancer cells are needed. Selenium, a proven anticarcinogen, gains due importance in terms of its efficacy to combat the side effects of cancer therapy. This study is a comparative analysis of the chemoprotective effects of selenium compounds, methyl selenol (generated from organic selenomethionine (5mmol/L ; METase 40U/L)) and sodium selenite (inorganic form)($30{\mu}M$) in peripheral blood human lymphocytes exposed to cisplatin and mitomycin. Biochemical alterations occurring in many cells during apoptosis include loss of plasma membrane phospholipid asymmetry, DNA fragmentation, and activation of caspase-3. The present study demonstrated that the selenium metabolite and selenite are efficient in protecting lymphocytes undergoing DNA damage and exerted their activity by reducing caspase 3 expression. Interestingly organic methylselenol (MeSe) was found to offer more protective effects compared to inorganic selenite (SeL), by reducing the induction of apoptosis by the cytotoxic agents. This suggests that MeSe and to a lesser extent selenite might have potential for assessment in clinical trials and could be considered as strong candidates in pharmacogenomics or in the nutriprotective arena.

Data Mining for High Dimensional Data in Drug Discovery and Development

  • Lee, Kwan R.;Park, Daniel C.;Lin, Xiwu;Eslava, Sergio
    • Genomics & Informatics
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    • v.1 no.2
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    • pp.65-74
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    • 2003
  • Data mining differs primarily from traditional data analysis on an important dimension, namely the scale of the data. That is the reason why not only statistical but also computer science principles are needed to extract information from large data sets. In this paper we briefly review data mining, its characteristics, typical data mining algorithms, and potential and ongoing applications of data mining at biopharmaceutical industries. The distinguishing characteristics of data mining lie in its understandability, scalability, its problem driven nature, and its analysis of retrospective or observational data in contrast to experimentally designed data. At a high level one can identify three types of problems for which data mining is useful: description, prediction and search. Brief review of data mining algorithms include decision trees and rules, nonlinear classification methods, memory-based methods, model-based clustering, and graphical dependency models. Application areas covered are discovery compound libraries, clinical trial and disease management data, genomics and proteomics, structural databases for candidate drug compounds, and other applications of pharmaceutical relevance.

Risk Assessment and Pharmacogenetics in Molecular and Genomic Epidemiology

  • Park, Sue-K.;Choi, Ji-Yeob
    • Journal of Preventive Medicine and Public Health
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    • v.42 no.6
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    • pp.371-376
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    • 2009
  • In this article, we reviewed the literature on risk assessment (RA) models with and without molecular genomic markers and the current utility of the markers in the pharmacogenetic field. Epidemiological risk assessment is applied using statistical models and equations established from current scientific knowledge of risk and disease. Several papers have reported that traditional RA tools have significant limitations in decision-making in management strategies for individuals as predictions of diseases and disease progression are inaccurate. Recently, the model added information on the genetic susceptibility factors that are expected to be most responsible for differences in individual risk. On the continuum of health care, from diagnosis to treatment, pharmacogenetics has been developed based on the accumulated knowledge of human genomic variation involving drug distribution and metabolism and the target of action, which has the potential to facilitate personalized medicine that can avoid therapeutic failure and serious side effects. There are many challenges for the applicability of genomic information in a clinical setting. Current uses of genetic markers for managing drug therapy and issues in the development of a valid biomarker in pharmacogenetics are discussed.

Study on the Medical Review on Yukjagyeol and Younggamudo Its Clinical Application (육자결(六字訣)과 영가무도(詠歌舞蹈)의 한의학적 고찰 및 임상적용에 대한 연구)

  • Lee, Dong-Wook;Han, Chang-Hyun;Park, Soo-Jin;Kwon, Young-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.3
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    • pp.516-527
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    • 2008
  • Sounds and music have been used in various ways in the East and the West, as it is well known that they influence the human mind and health a lot. Recently, there have been many studies regarding the remedy through sounds and music in the West and they have made good effects in the actual therapy. In the East, people knew that sounds and music would make great effects on human mind long time ago and they placed importance on sounds and music. Although there is a Sound Therapy in Oriental Medicine, it is not studied sufficiently in modern Oriental Medicine. It does not have clear standards for the clinical application and has not been frequently used. Accordingly, Yukjagyeol which has long been used in Korean Medicine and Younggamudo which was made by Kim Il-bu in late Chosun were compared from the perspective of acoustics and demonstrative treatment theory of Korean Medicine. Younggamudo by Kim il-bu allot the five sounds such as 'Eum, Ah, Eo, Ih and Uh' to 'spleen, lung, liver, heart and kidney' respectively. As the five sounds are all vowels and vibrate the vocal band as much as possible, they vibrate and resonant the respective organs to help them to function and promote circulation. In oriental medicine, there is 'Singing and Dancing Treatment'. They say songs and dances nurtures personality, supplement blood stream and comfort the mind. As the five sounds of Younggamudo take the melody while vibrating the vocal band sufficiently, when it passes from Youngto Ga(Songs) we may dance moving our bodies according to the rhythm. Therefore Gongbeop of Younggamudo helps the functionality of human organs and promotes blood circulation. As Yukjagyeol is Sabeop(discharging method), it should be used for those who have surplus Sagi and should not use for Heojeung. As Younggamudo is Bobeop(supplementing method), it is not for Shiljeung but for Heojeung which lacks of Jeonggi. It is considered that healthy people without specific disease can use it as a preventive method of 'Chimijeong' to maintain their physical and mental health. It is considered that we can have useful effects if we apply Yukjagyeol and Younggamudo dialectically with the concept of Bosa. It is considered that concrete application to Sound Gigong can be possible by searching for the methodology for empirical further study and clinical experiments and clinical application in the future.

The anti-hyperglycemic property of different ginseng partitions

  • Xie, Jing-Tian;Wang, Chong-Zhi;Kim, Stephen;Yuan, Chun-Su
    • Advances in Traditional Medicine
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    • v.5 no.1
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    • pp.1-15
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    • 2005
  • Ginseng is a popular medicinal plant highly valued throughout the world. Asian ginseng is one of the most common species of ginseng. It has long occupied a significant position in oriental medicine and has been justified its name as the 'king herb'. As a nutritional supplement, ginseng is an extremely common and popular herbal medicine in the United States and Canada in recent decades. The multiple constituents of ginseng possess equally multifaceted pharmacological actions as demonstrated by numerous studies. Ginseng root and its constituents influenced the central nervous system, endocrine, cardiovascular, gastrointestinal system, sexual, renal organ and immune system, etc. One important action is its anti-hyperglycemic effect. Previous studies on ginseng demonstrate that only the root of ginseng has been used in the treatment of diabetes, while the other parts of ginseng plant were always neglected. Recently, we analyzed the constituents of ginseng berry, leaf and discovered that ginseng berry, leaf extracts and its total ginsenosides have the ability to reduce hyperglycemia and body weight and increase the peripheral glucose utilization in obese or diabetic ob/ob or db/db mice. Our data suggest that all parts of ginseng plant, including root, berry, leaf and stem exhibit potent anti-hyperglycemic and anti-obese effects and may provide an opportunity to develop a novel class of anti-diabetic agents.

Effects of Panax notoginseng, ginsenoside Rb1, and notoginsenoside R1 on proliferation of human breast carcinoma MCF-7 cells

  • Xie, Jing-Tian;Aung, Han H;Wang, Chong Zhi;Mehendale, Sangeeta R;McEntee, Eryn;Wicks, Sheila;Li, Jing;Yuan, Chun-Su
    • Advances in Traditional Medicine
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    • v.6 no.4
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    • pp.286-292
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    • 2006
  • In this study, we evaluated the antiproliferative effects of Panax notoginseng, ginsenoside Rb1, and notoginsenoside R1 in the human breast carcinoma MCF-7 cell line. Our results indicated that both Panax notoginseng radix extract (NRE) and Panax notoginseng rhizoma extract (NRhE) possess significant antiproliferative activities in MCF-7 cells. Compared to control group (100%), at the concentrations of 0.05, 0.5, and 1.0 mg/ml NRE, cell growth was concentration-dependently reduced to 81.0 ${\pm}$ 6.1 (P < 0.01), 34.2 ${\pm}$ 4.8 (P < 0.001), and 19.3 ${\pm}$ 1.9 (P < 0.001), respectively. Similar results with NRhE at concentrations of 0.5 and 1.0 mg/ml were obtained in these MCF-7 cells. To identify the responsible chemical constituent, we tested the antiproliferation effects of two representative saponins, ginsenoside Rb1 and notoginsenoside R1, on the MCF-7 cells. The data showed that ginsenoside Rb1 was endowed with antiproliferative properties, while notoginsenoside R1 did not have an inhibitory effect in the concentrations tested. Our studies provided evidence that Panax notoginseng extracts and ginsenoside Rb1 may be beneficial, as adjuvants, in the treatment of human breast carcinoma.

The Use of Pharmacogenomic Method for the Prediction of Antidepressant Responsiveness (약리 유전학적 방법을 이용한 항우울제 치료반응성의 예측)

  • Kim, Doh Kwan;Lim, Shinn-Won
    • Korean Journal of Biological Psychiatry
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    • v.9 no.1
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    • pp.25-33
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    • 2002
  • Serotonin transporter(5-HTT) is one of the major action site of antidepressants in neuronal cells. According to the recent studies, it is known that the functional polymorphism in the promoter region of the 5-HTT gene(5-HTT linked polymorphism repetitive element in promoter region, 5-HTTLPR) is associated with antidepressant responsiveness, and the distributions of 5-HTTLPR is various among the different populations. Our preliminary study suggested that it is possible to measure the endophenotype of 5-HTTLPR genotype by examining the pharmacodynamic research of the 5-HTT in platelet membranes. However, there are limitations to predicting the antidepressant responsiveness only from the endophenotypic characteristics of 5-HTT gene promoter polymorphism, and therefore we propose to use the pharmacogenomic methods for overcoming these limitations. We found that the significant correlations existed among the genetic polymorphisms of biogenic amine transporters whose structure and characteristics are similar to the 5-HTT, and the predictable odds ratio of antidepressant responsiveness are increased significantly by combining the effect with other associated polymorphisms, compared to the effect of 5-HTT promoter polymorphism only. These results support the hypothesis that antidepressant treatment has to be individualized according to the genetic and ethnic background of depressed patients. It would be possible to develope the evaluation tools to predict the antidepressant responsiveness and its side effect profile, if scientists reveal the genes related to the action mechanism as well as the metabolism of antidepressants so as to discover the interaction of those genes and contribution of endogenotypes toward antidepressant responsiveness.

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